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Encyclopedia > Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide
Identifiers
CAS number 53-84-9
PubChem 925
MeSH Nicotinamide-Adenine+Dinucleotide
Properties
Molecular formula C21H27N7O14P2
Molar mass 663.425
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Infobox disclaimer and references

Nicotinamide adenine dinucleotide (NAD+ or in older notation DPN+) is an important coenzyme found in cells. It plays key roles as a carrier of electrons and a participant in metabolic redox reactions, as well as in cell signaling.[1][2] There are two forms of this coenzyme in cells, NAD+ and the phosphorylated form NADP+. These two related coenzymes have similar chemistry, but perform different roles in metabolism. When both coenzymes are being discussed, they are referred to collectively as NAD(P)+. Image File history File links NAD+_phys. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... PubChem is a database of chemical molecules. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... A chemical formula is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... For other uses, see Carbon (disambiguation). ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... General Name, symbol, number phosphorus, P, 15 Chemical series nonmetals Group, period, block 15, 3, p Appearance waxy white/ red/ black/ colorless Standard atomic weight 30. ... Molar mass is the mass of one mole of a chemical element or chemical compound. ... The plimsoll symbol as used in shipping In chemistry, the standard state of a material is its state at 1 bar (100 kilopascals exactly). ... Coenzyme A Coenzymes are small organic non-protein molecules that carry chemical groups between enzymes. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... Illustration of a redox reaction Redox (shorthand for oxidation/reduction reaction) describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed. ... Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. ... Nicotinamide adenine dinucleotide phosphate (NADP) is used in anabolic reactions, such as fatty acid and nucleic acid synthesis, which require NADPH as a reducing agent. ...


NADH is the reduced form of NAD+, and NADPH is the reduced form of NADP+. In metabolism, NAD+ and NADP+ are used as oxidizing agents - they accept electrons from other molecules, whereas NADH and NADPH are reducing agents that donate electrons. In chemical terms, the coenzymes are reactants in hydride transfer reactions. These redox reactions are the primary function of NAD(P)+. However, these coenzymes are also used in a range of metabolic processes that do not involve redox reactions, such as second messenger systems and posttranslational modifications. Illustration of a redox reaction Redox (shorthand for oxidation/reduction reaction) describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed. ... European Union Chemical hazard symbol for oxidizing agents Dangerous goods label for oxidizing agents Oxidizing agent placard An oxidizing agent (also called an oxidant or oxidizer) is A chemical compound that readily transfers oxygen atoms or A substance that gains electrons in a redox chemical reaction. ... A reducing agent (also called a reductant or reducer) is the element or a compound in a redox (reduction-oxidation) reaction (see electrochemistry) that reduces another species. ... Hydride is the name given to the negative ion of hydrogen, H−. Although this ion does not exist except in extraordinary conditions, the term hydride is widely applied to describe compounds of hydrogen with other elements, particularly those of groups 1–16. ... In cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signalling where the signalling molecule does not enter the cell, but rather utilizes a cascade of events that transduces the signal into a cellular change. ... Posttranslational modification is the chemical modification of a protein after its translation. ...


NAD+ can be synthesised from amino acids such as tryptophan. Alternatively, fragments of the coenzyme taken up in the diet or released by reactions that break down the structure of NAD+ can be salvaged and then recycled back into the active form. Due to the central role of these coenzymes in metabolism, the enzymes involved in making and using NAD(P)+ have been described as promising targets for drug discovery.[3] This may be particularly important in the development of future drugs to exploit the roles of NAD+ in the regulation of aging and longevity.[4] Tryptophan is an essential amino acid involved in human nutrition. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... In medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered and/or designed. ... Ageing or aging is the process of getting older. ... Longevity is a term that generally refers to long life or great duration of life.[1] Reflections on longevity have usually gone beyond acknowledging the basic shortness of human life and have included thinking about methods to extend life. ...

Contents

Physical and chemical properties

Nicotinamide adenine dinucleotide consists of two ribose rings, one with adenine attached to its 1' carbon atom and the other with nicotinamide at this position; these two sugar-heterocycle moieties are joined together by a bridge of two phosphate groups through the 5' carbons. In NADP+, the ribose ring attached to the adenine has an additional phosphate group at the 2' position. Ribose Ribose, primarily seen as D-ribose, is an aldopentose — a monosaccharide containing five carbon atoms, and including an aldehyde functional group. ... For the programming language Adenine, see Adenine (programming language). ... Nicotinamide, also known as niacinamide, is the amide of niacin (vitamin B3) which has the chemical formula C6H6N2O. Niacinamide is a derivative of vitamin B-3 can be used for the treatment of arthritis by aiding the body in its production of cartilage. ... Heterocycles are organic chemical structures containing non-carbon elements. ... A phosphate, in inorganic chemistry, is a salt of phosphoric acid. ...


In appearance, these coenzymes are white amorphous hygroscopic powders that are highly water-soluble.[5] These solids are stable if stored dry and in the dark. Solutions of NAD(P)+ are colorless and stable for about a week at 4°C at neutral pH, but decompose rapidly in acids. Upon decomposition, they form products that are enzyme inhibitors.[6] Wax and paraffin are amorphous. ... Hygroscopy is the ability of a substance to attract water molecules from the surrounding environment through either absorption or adsorption. ... HIV protease in a complex with the protease inhibitor ritonavir. ...

The reduction of NAD(P)+ to NAD(P)H.

NAD(P)+ absorbs strongly in the ultraviolet due to the adenine base. Peak absorption is at 259 nm, with a extinction coefficient of 16,900 M-1 cm-1. The reduced forms of NAD(P)H also absorb at a higher wavelength, with a second peak in UV absorption at 339 nm that has an extinction coefficient of 6,220 M-1 cm-1.[7] This difference in the ultraviolet absorption spectrums between the oxidised and reduced forms of the coenzymes makes it simple to measure the conversion of one to another in enzyme assays - by measuring the amount of UV absorption at 339 nm using a spectrophotometer. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... For other uses, see Ultraviolet (disambiguation). ... For the programming language Adenine, see Adenine (programming language). ... A nanometre (American spelling: nanometer) is 1. ... A substance or object that is opaque is neither transparent nor translucent. ... A materials absorption spectrum shows the fraction of incident electromagnetic radiation absorbed by the material over a range of frequencies. ... Enzyme assays are laboratory methods for measuring enzymatic activity. ... Spectrophotometer In physics, spectrophotometry is the quantitative study of electromagnetic spectra. ...


Cells use NAD(P)+ to accept or donate electrons in redox reactions. During these reactions the reductant RH2 is oxidised and NAD(P)+ reduced to NAD(P)H.

RH2 + NAD(P)+ → NAD(P)H + H+ + R

The above reaction involves the removal of two hydrogen atoms in the form of a hydride ion and a proton H+ from the reactant R. The proton is released into solution. From the hydride electron pair, one electron is transferred to the positively-charged nitrogen of the nicotinamide ring of NAD(P)+, and the other hydrogen transferred to the carbon atom opposite this nitrogen. Hydride is the name given to the negative ion of hydrogen, H−. Although this ion does not exist except in extraordinary conditions, the term hydride is widely applied to describe compounds of hydrogen with other elements, particularly those of groups 1–16. ... This article is about the electrically charged particle. ...

Image File history File links Size of this preview: 546 × 599 pixelsFull resolution (1002 × 1100 pixel, file size: 255 KB, MIME type: image/png) File historyClick on a date/time to view the file as it appeared at that time. ... armchair conformational isomerism of Cyclohexane. ... Image File history File links Size of this preview: 475 × 599 pixelsFull resolution (872 × 1100 pixel, file size: 243 KB, MIME type: image/png) File historyClick on a date/time to view the file as it appeared at that time. ... Image File history File links Download high-resolution version (986x1100, 284 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Enzyme Nicotinamide adenine dinucleotide User:Benjah-bmm27/Gallery User:Ben Mills/Gallery ... This is a calotte model of cyclohexane. ...

Biosynthesis

NAD+ is synthesized through two main types of metabolic pathway. In the first type, it is produced from amino acids in a de novo pathway, while in salvage pathways, preformed components such as nicotinamide are recycled back to NAD+. Phenylalanine is one of the standard amino acids. ... In general usage, de novo is a Latin expression meaning afresh, anew, beginning again. In USA Banking, a de novo bank is defined as a state member bank that has been in operation for five years or less. ... Nicotinamide, also known as niacinamide, is the amide of niacin (vitamin B3) which has the chemical formula C6H6N2O. Niacinamide is a derivative of vitamin B-3 can be used for the treatment of arthritis by aiding the body in its production of cartilage. ...


De novo production

Metabolic pathways that synthesize and consume NAD+. The abbreviations are defined in the text.

Most organisms can synthesize NAD(P) from simple components. The exact set of reactions differ among organsisms, but a common feature is the generation of quinolinic acid (QA) from an amino acid - either tryptophan (Trp) in animals and some bacteria, or aspartic acid in some bacteria and plants.[8] The quinolinic acid is converted to nicotinic acid mononucleotide (NaMN) by transfer of a phosphoribose moiety. An adenyl group is then transferred to form nicotinic acid adenine dinucleotide (NaAD). Finally, the nicotinic acid group in NaAD is amidated to an nicotinamide (Nam) group, forming nicotinamide adenine dinucleotide.[1] Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... In biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. ... Tryptophan is an essential amino acid involved in human nutrition. ... Aspartic acid (abbreviated as Asp or D; Asx or B represent either aspartic acid or asparagine[1] ) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CO2H. The L-isomer is a protonated varient of one of the 20 proteinogenic amino acids, i. ... Amide functional group Amides possess a conjugated system spread over the O, C and N atoms, consisting of molecular orbitals occupied by delocalized electrons. ...


In a further step, some NAD+ is converted into NADP+ by NAD+ kinase, which phosphorylates NAD+.[9] In most organisms, this enzyme uses ATP as the source of the phosphate group, while in some bacteria such as Mycobacterium tuberculosis and archaea such as Pyrococcus horikoshii, inorganic polyphosphate acts as an alternative phosphate donor.[10][11] NAD+ kinase (EC 2. ... Binomial name Zopf 1883 Mycobacterium tuberculosis is the bacterium that causes most cases of tuberculosis. ... Phyla Crenarchaeota Euryarchaeota Korarchaeota Nanoarchaeota ARMAN The Archaea (), or archaebacteria, are a major group of microorganisms. ... Species P. furiosus Synonyms Pyrococcus Fiala and Stetter 1986 In taxonomy, Pyrococcus is a genus of the Thermococcaceae. ... Polyphosphates are phosphate polymers linked between hydroxyl groups and hydrogen atoms. ...

Salvage pathways use three precursors for NAD+.
Salvage pathways use three precursors for NAD+.

Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ...

Salvage pathways

As well as forming NAD+ from simple amino acid precursors, cells also use preformed nicotinamide moieties. These are either taken up from the diet (in the form of vitamin B3, also called niacin), or produced within cells when the nicotinamide moiety is released from NAD+ in ADP-ribose transfer reactions. The three compounds that contain the nicotinamide ring and are used in these salvage metabolic pathways are nicotinic acid, nicotinamide and nicotinamide riboside. These precursors are fed into the main biosynthetic pathway, shown above, through adenylation and phosphoribosylation reactions.[1] Some pathogens, such as the yeast Candida glabrata and the bacterium Haemophilus influenzae are NAD+ auxotrophs and are entirely dependent on nicotinamide salvage pathways.[12][13] Niacin, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. ... Binomial name Candida glabrata (Anderson) Meyer & Yarrow Candida glabrata is a haploid yeast of the genus Candida, previously known as Torulopsis glabrata. ... Binomial name Haemophilus influenzae (Lehmann & Neumann 1896) Winslow 1917 Haemophilus influenzae, formerly called Pfeiffers bacillus or Bacillus influenzae, is a non-motile Gram-negative coccobacillus first described in 1892 by Dr. Richard Pfeiffer during an influenza pandemic. ... Auxotrophy is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). ...


Despite the presence of the de novo pathway, these salvage reactions are essential in humans: with a lack of niacin in the diet causing the vitamin deficiency disease pellagra.[14] This high requirement for NAD+ is the result of the constant consumption of the coenzyme in signaling reactions, since the cycling of NAD+ between oxidized and reduced forms during redox reactions causes no change in the overall levels of the coenzyme. Pellagra is a vitamin deficiency disease caused by dietary lack of niacin (vitamin B3) and protein, especially proteins containing the essential amino acid tryptophan. ...


Functions

Nicotinamide adenine dinucleotide is an essential part of metabolism. In rat liver, the total amount of NAD+ and NADH is approximately 1 μmol-1 g wet weight, with about 10-fold less NADP+ and NADPH.[15] The actual concentration of NAD+ in cell cytoplasm is hard to measure, with recent estimates in red blood cells ranging around 300 μM.[16][17] However, over 80% of NADH is bound to proteins, so the concentration of free coenzymes is much lower.[18] “Red cell” redirects here. ...


The balance between the oxidised and reduced forms of nicotinamide adenine dinucleotide is called the NAD+/NADH ratio. This ratio reflects the redox state of a cell, which controls both the metabolic activity and the health of that cell. Several key enzymes are controlled by the NAD+/NADH ratio, including glyceraldehyde 3-phosphate dehydrogenase and pyruvate dehydrogenase.[4] In healthy mammalian tissues, estimates of the NAD+/NADH ratio range around 1, so the concentrations of NAD+ and NADH are roughly comparable.[4] In contrast, the NADP+/NADPH ration is about 0.005, around 200 times lower than the NAD+/NADH ratio, so NADPH is the dominant form of this coenzyme.[19] These different ratios reflect the different metabolic roles of NADH and NADPH. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is an important enzyme used in reaction 6 of glycolysis. ... Pyruvate dehydrogenase is an enzyme (E1) in the pyruvate dehydrogenase complex (PDC). ...


Role in redox metabolism

A simplified outline of redox metabolism, showing the linking role of NAD(P)+ between the citric acid cycle and oxidative phosphorylation.
A simplified outline of redox metabolism, showing the linking role of NAD(P)+ between the citric acid cycle and oxidative phosphorylation.
Further information: Metabolism

The main role of NAD(P)+ in metabolism is the transfer of electrons from one redox reaction to another. This is most important in the release of energy from nutrients. Here, reduced compounds such as glucose are oxidized, releasing energy. The energy is transferred to NAD+ by reducing this to NADH, as part of glycolysis and the citric acid cycle. The NADH is then oxidized in turn by the electron transport chain, which pumps protons across a membrane and generates ATP through oxidative phosphorylation.[20] Since the oxidized and reduced forms of nicotinamide adenine dinucleotide are both used in these linked sets of reactions, the cell maintains approximately equal concentrations of NAD+ and NADH; the high NAD+/NADH ratio allows this coenzyme to act as both an oxidizing and a reducing agent.[21] In contrast, the main role of the phosphorylated form of this coenzyme is as a reducing agent in anabolism, so the NADP+/NADPH ratio is kept very low, allowing NADPH to drive redox reactions as a strong reducing agent.[21] Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... A few of the metabolic pathways in a cell. ... Overview of the citric acid cycle The citric acid cycle (also known as the tricarboxylic acid cycle, the TCA cycle, or the Krebs cycle, after Hans Adolf Krebs who identified the cycle) is a series of chemical reactions of central importance in all living cells that use oxygen as part... The Electron Transport Chain. ... A few of the metabolic pathways in a cell. ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... The word glycolysis is derived from Greek γλυκύς (sweet) and λύσις (rupture). ... Overview of the citric acid cycle The citric acid cycle (also known as the tricarboxylic acid cycle, the TCA cycle, or the Krebs cycle, after Hans Adolf Krebs who identified the cycle) is a series of chemical reactions of central importance in all living cells that use oxygen as part... The Electron Transport Chain. ... The Electron Transport Chain. ... Anabolism is the metabolic process that builds larger molecules from smaller ones. ...


Although it is most important in catabolism, NADH is also used in a few anabolic reactions, such as gluconeogenesis.[22] This poses a problem for prokaryotes growing on nutrients that release only a small amount of energy upon oxidation. For example, nitrifying bacteria such as Nitrobacter oxidize nitrite to nitrate, donating the electrons to oxygen. The energy released in this reaction is enough to pump protons and generate ATP, but not enough to produce NADH directly.[23] Since the cells still require NADH for anabolic reactions, they use a nitrite oxidoreductase to produce enough proton-motive force to run part of the electron transport chain in reverse, making it generate NADH.[24][25] Pyruvic acid Oxaloacetic acid Phosphoenolpyruvate Fructose 1,6-bisphosphate Fructose 6-phosphate Glucose-6-phosphate Glucose Gluconeogenesis is the generation of glucose from non-sugar carbon substrates like pyruvate, lactate, glycerol, and amino acids (primarily alanine and glutamine). ... Nitrogen cycle Nitrification is the biological oxidation of ammonia with oxygen into nitrite followed by the oxidation of these nitrites into nitrates. ... Nitrobacter is a rod-shaped bacteria, which is an important part of the nitrogen cycle. ... Nitrite oxidoreductase (NOR or NXR) is an enzyme involved in nitrification. ... Chemiosmosis is the diffusion of ions across a membrane. ...


Non-redox roles

The coenzyme NAD+ can also be consumed by in ADP-ribose transfer reactions. For example, some enzymes add the ADP-ribose moiety of this molecule to proteins, in a posttranslational modification called ADP-ribosylation.[26] These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.[27] ADP-ribose can also be transferred to proteins in long branched chains, in a reaction called poly(ADP-ribosyl)ation.[28] This protein modification is carried out by the poly ADP-ribose polymerases.[28][29] The poly(ADP-ribose) structure is involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance.[29] Posttranslational modification is the chemical modification of a protein after its translation. ... ADP ribose ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties. ... Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. ... DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. ... A section of mouse liver showing an apoptotic cell indicated by an arrow Apoptosis (pronounced apo tō sis) is a process of suicide by a cell in a multicellular organism. ... Poly (ADP-ribose) polymerase (PARP) is a protein involved in a number of cellular processes involving mainly DNA repair and programmed cell death. ... HeLa cells stained for DNA with the Blue Hoechst dye. ... DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. ... A telomere is a region of highly repetitive DNA at the end of a chromosome that functions as a disposable buffer. ...


Other NAD-dependent enzymes include bacterial DNA ligases, which join two DNA ends by using NAD as a substrate to donate an AMP group to the 5' phosphate of one DNA end; this intermediate is then attacked by the 3' hydroxyl group of the other DNA end, forming a new phosphodiester bond.[30] This is in contrast to eukaryotic DNA ligases, which use ATP to form the DNA-AMP intermediate. NAD+ is also consumed by sirtuins, which are NAD-dependent deacetylases, such as Sir2.[31] These enzymes act by transferring an acetyl group from their substrate protein to the ADP-ribose moiety of NAD+; this cleaves the coenzyme and releases nicotinamide and O-acetyl-ADP-ribose. The sirtuins seem to be mainly involved in regulating transcription through deacetylating histones and altering nucleosome structure.[32] It has been suggested that sticky end/blunt end be merged into this article or section. ... Diagram of phosphodiester bonds between nucleotides A phosphodiester bond is a group of strong covalent bonds between the phosphorus atom in a phosphate group and two other molecules over two ester bonds. ... Kingdoms Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. ... Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ... Sirtuin is a class of NAD-dependent histone deacetylases (class 3) in both prokaryotes (organisms without a membrane for their cells nucleus) and eukaryotes (organisms whose cells nucleus have a membrane). ... Sir2 (whose homology in mammals is SIRT1, SIR2L1 or Sir2α) is a member of a family of closely related enzymes, the sirtuins. ... Acetyl is the radical of acetic acid. ... A micrograph of ongoing gene transcription of ribosomal RNA illustrating the growing primary transcripts. ... A nucleosome is a unit made of DNA and histones. ...


NAD+ can also be converted into cyclic ADP-ribose by ADP-ribosyl cyclases as part of a second messenger system.[33] The cyclic ADP ribose second messenger molecule acts in calcium signaling by releasing calcium from intracellular stores.[34] It does this by binding to and opening a class of calcium channels called ryanodine receptors. Cyclic ADP Ribose popularly known as cADPR is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5 OH of the adenosine (like ADP), further connected to another ribose at the 5 position which in turn closes the cycle by glycosidic bonding to the Nitrogen1 of the... In cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signalling where the signalling molecule does not enter the cell, but rather utilizes a cascade of events that transduces the signal into a cellular change. ... Calcium ions act as second messengers in signal transduction. ... Ryanodine receptors form a class of calcium channels in various forms of muscle. ...


Binding to proteins

An example of the Rossmann fold, a structural domain of a decarboxylase protein from the bacterium Staphylococcus epidermidis (PDB ID 1G5Q) with the bound flavin mononucleotide cofactor shown.
An example of the Rossmann fold, a structural domain of a decarboxylase protein from the bacterium Staphylococcus epidermidis (PDB ID 1G5Q) with the bound flavin mononucleotide cofactor shown.
Further information: Protein structure and Oxidoreductases

NAD(P)+ and NAD(P)H bind to a structural motif named the Rossmann fold.[35] This motif is found in many proteins that bind nucleotides. The structure is composed of three or more parallel beta strands linked by two alpha helices in the topological order beta-alpha-beta-alpha-beta. Because each Rossmann fold binds one nucleotide, binding domains for the dinucleotide NAD+ consists of two paired Rossmann folds, with each fold binding one nucleotide moiety of the cofactor. Single Rossmann folds are found in proteins that bind mononucleotides, such as the cofactor FMN. The motif is named after Michael Rossmann who was the first scientist to notice that this structure was a frequently-occurring motif in nucleotide binding proteins.[36] However, this motif is not universal among NAD(P)-dependent enzymes, since a class of bacterial enzymes have recently been discovered that bind NAD(P)+ but lack Rossmann folds.[37] Image File history File links Download high-resolution version (851x734, 232 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Adenosine triphosphate Rossmann fold ... Image File history File links Download high-resolution version (851x734, 232 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Adenosine triphosphate Rossmann fold ... Within a protein, a structural domain (domain) is an element of overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. ... Carboxy-lyases, also known as decarboxylases, are carbon-carbon lyases that add or remove a carboxyl group from organic compounds. ... Binomial name (Winslow & Winslow 1908) Evans 1916 Staphylococcus epidermidis is a member of the bacterial genus Staphylococcus, consisting of Gram-positive cocci arranged in clusters. ... Flavin mononucleotide or FMN is derived from riboflavin (vitamin B2) and functions as cofactor of various oxidoreductases. ... Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen, and sulfur. ... In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule (the oxidant, also called the hydrogen donor or electron donor) to another (the reductant, also called the hydrogen acceptor or electron acceptor). ... In an unbranched, chain-like biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or fold within the chain, which appears also in a variety of other molecules. ... An example of the Rossmann fold, a structural domain of a decarboxylase protein from the bacterium Staphylococcus epidermidis (PDB ID 1G5Q) with the bound flavin mononucleotide cofactor shown. ... A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ... Diagram of β-pleated sheet with H-bonding between protein strands The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins — the first is the alpha helix — consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. ... Side view of an α-helix of alanine residues in atomic detail. ... Flavin mononucleotide or FMN is derived from riboflavin (vitamin B2) and functions as cofactor of various oxidoreductases. ... Michael Rossmann is a British chemist and a Fellow of the Royal Society. ...


Despite this similarity in how proteins bind NAD+ and NADP+, enzymes almost always show a high level of specificity for either one or the other of these coenzymes.[38] This specificity is due to the distinct metabolic roles of the two conezymes and results from distinct sets of amino acid residues in the coenzyme-binding pocket. For example, in the active site of NADP-dependent enzymes, a specific ionic bond is formed between a basic amino acid side chain and the acidic phosphate group of NADP+. Conversely, in NAD-dependent enzymes the charge in this pocket is reversed, preventing NADP+ binding. There are a few exceptions to this general rule, and enzymes such aldose reductase, glucose-6-phosphate dehydrogenase and methylenetetrahydrofolate reductase show dual-cofactor specificity in some species.[39] Phenylalanine is one of the standard amino acids. ... Electron configurations of lithium and fluorine. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... see Glucose-6-phosphate_dehydrogenase_deficiency Category: Biochemistry stubs ... Methylenetetrahydrofolate reductase (MTHFR) is an enzyme (EC 1. ...


History

The coenzyme NAD+ was first discovered by Arthur Harden and William Youndin 1906.[40] They noticed that adding boiled and filtered yeast extract greatly accelerated alcoholic fermentation in unboiled yeast extracts. They called the unidentified factor responsible for this effect a coferment. Through a long and difficult purification from yeast extracts, this heat-stable factor was identified as a nucleotide sugar phosphate by Hans von Euler-Chelpin.[41] Later, in 1936, Otto Heinrich Warburg identified the function of the nucleotide in hydride transfer.[42] Arthur Harden (October 12, 1865 – June 17, 1940) was an English biochemist. ... Typical divisions Ascomycota (sac fungi) Saccharomycotina (true yeasts) Taphrinomycotina Schizosaccharomycetes (fission yeasts) Basidiomycota (club fungi) Urediniomycetes Sporidiales Yeasts are a growth form of eukaryotic microorganisms classified in the kingdom Fungi, with approximately 1,500 species described. ... Pyruvic acid becomes ethanol (alcohol) and carbon dioxide by using the hydrogen ions and electrons from NADH. Again, this occurs in the cytosol of the cell. ... A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ... Hans Karl August Simon von Euler-Chelpin (February 15, 1873 – November 6, 1964) was a Swedish (German-born) biochemist. ... Otto Heinrich Warburg (October 8, 1883, Freiburg im Breisgau – August 1, 1970, Berlin), son of Emil Warburg, was a German physiologist and medical doctor. ...


In the early 1940s, Arthur Kornberg made an important contribution towards understanding NAD(P) metabolism by being the first to isolate an enzyme in the biosynthetic pathway.[43] Subsequently, in 1949, Morris Friedkin and Albert L. Lehninger proved that NADH linked metabolic pathways such as the citric acid cycle with the synthesis of ATP in oxidative phosphorylation.[44] Arthur Kornberg Arthur Kornberg (born March 3, 1918) is an American biochemist who won the Nobel Prize in Physiology or Medicine 1959 for his discovery of the mechanisms in the biological synthesis of deoxyribonucleic acid (DNA) together with Dr. Severo Ochoa of New York University. ... Albert Lester Lehninger (February 17, 1917 - March 4, 1986) was an American biochemist, and is widely regarded as a pioneer in the field of bioenergetics. ...


See also

For the programming language Adenine, see Adenine (programming language). ... A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ... Niacin, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. ...

References

  1. ^ a b c Belenky P, Bogan KL, Brenner C (2007). "NAD+ metabolism in health and disease". Trends Biochem. Sci. 32 (1): 12-9. PMID 17161604. 
  2. ^ Pollak N, Dölle C, Ziegler M (2007). "The power to reduce: pyridine nucleotides--small molecules with a multitude of functions". Biochem. J. 402 (2): 205-18. PMID 17295611. 
  3. ^ Khan JA, Forouhar F, Tao X, Tong L (2007). "Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery". Expert Opin. Ther. Targets 11 (5): 695-705. PMID 17465726. 
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  • NAD and NADP
  • Nicotinamide

 
 

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